Background Glucocorticoid is a common drug for treatment of thyroid-associated ophthalmopathy (TAO) with good effectiveness.But some adverse reactions of glucocorticoid are inevitable.At recent years,99technetium-methylene bisphosphonate(99Tc-MDP) is being paid more and more attentions in the treatment of TAO,but its effectiveness and safety is worthy of comparison to traditional treatment methods.Objective This study was to evaluate the efficacy of treatment with intravenous injection of 99Tc-MDP for TAO.Methods The Cochrane Library,CNKI,PubMed,Wanfang database,Weipu net were searched in computer and Google Scholar was searched manually.The randomized controlled trail (RCT) of intravenous injection of 99Tc-MDP for TAO were collected from establishment of database through April,2012.The quality of included literature was assessed based on the methodology of the study.The evaluating indexes included the primary treating outcomes,such as total efficacy,exophthalmic extent and recurrence rate as well as secondary outcomes such as adverse effect.RevMan 5.1 software was used for Mate analysis.Results A total of 11 RCTs were identified with 706 patients.Subgroup analysis was carried out based on the outcome measures and intervention.No significant difference was found in the overall effective rate between intravenous injection of 99Tc-MDP and immunosuppressive treatment (RR =0.96,95 ％ CI:0.76 to 1.22,P=0.740).However,the effective rate was significant different between intravenous injection of 99Tc-MDP and oral prednisone (RR =1.25,95 ％ CI:1.06-1.46,P =0.007) or between intravenous injection of 99 Tc-M DP and the blank control group (RR =2.53,95 ％ CI:1.68-3.81,P =0.000).Significant difference also was found in the total effective rate between intravenous injection of 99Tc-MDP with methyprednisone and methyprednisone alone (RR =1.27,95％ CI:1.05-1.53,P =0.010).There were significant differences in the effective rate of proptosis between intravenous injection of 99Tc-MDP and oral prednisone (RR=2.02,95％ CI:1.44-3.56,P=0.020).The recurrence rate of TAO was significant different between intravenous injection of 99Tc-MDP and oral prednisone (RR =0.51,95％ CI:0.33-0.78,P=0.002).Less adverse responses were seen in the intravenous injection of 99Tc-MDP group than the oral prednisone group and immunosuppressive treatment group.Conclusions Intravenous injection of 99Tc-MDP for TAO appears to be of a similar effectiveness to immunosuppressive method.The combination of intravenous injection of 99Tc-MDP with methyprednisone seems to be more effective than methyprednisone alone,with little systemic adverse effect after application.

Ten glycosidic compounds were isolated from an ethanol extract of Machilus wangchiana by a combination of various chromatographic techniques including column chromatography over silica gel and Sephadex LH-20 and reversed-phase flash chromatography and HPLC. Their structures were identified by spectroscopic data analysis (IR, MS, and NMR) as icariside B1 (1), boscialin-3-O-β-D-glucopyranoside (2), pisumionoside (3), isolariciresinol-9'-O-β-D-xylopyranoside (4), 5'-methoxyisolariciresinol-9'-O-β-D-xylopyranoside (5), lyoniresinol-9'-O-β-D-xylopyranoside (6), (E) -4-hydroxyphenylprop-7-ene 4-O-β-D-glucopyranoside (7), (E) - 4-hydroxy-3-methoxyphenylprop-7-ene 4-O-α-L-rhamnopyranosyl-(1 --> 6) -β-D-glucopyranoside (8), 4-hydroxy-3-methoxyphenylprop-8-ene 4-O-β-D-xylopyraosyl-(1 --> 6) -β-D-glucopyranoside (9), and 4-hydroxy-3,5-dimethoxyphenylprop-8-ene 4-O-α-L-rhamnpyranosyl-(1 --> 6)-β-D- glucopyranoside (10), respectively.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Glycosides ; chemistry ; isolation & purification ; Lauraceae ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization

Objective To investigate T-bet mRNA expression on peripheral blood mononuclear cells (PBMCs) and its relations with allergen specific IgE (SIgE), eosinophile cationic protein (ECP) levels, and allergic symptom in patients with allergic rhinitis (AR). Methods The allergen, SIgE, and ECP in serum of patients with AR were detected by Unicap CAP system. Blood samples were taken from 15 healthy controls and 35 house dust mite allergic patients. PBMC was isolated by density gradient centrifugation and one part of them was cultured with mite allergen at a concentration of 50 μg/mL. PBMC was subjected to analysis of T-bet mRNA expression using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results The ratio of T-bet to β-actin mRNA levels was 0.418 ± 0. 101 in patients of AR and 0.706 ± 0.091 in healthy controls and the difference was significant (P ＜ 0.01). The expression intensity of T-bet mRNA was not related to varying severity of allergic symptom and ECP levels ( r = - 0.227, - 0.033, P ＞ 0.05). However, there was an inverse correlation between expression intensity of T-bet mRNA and SIgE concentration (r = -0.375, P ＜ 0.05). There was a positive correlation between SIgE and allergic symptom scores ( r = 0.426, P ＜ 0.05). After that PBMC was stimulated by mite allergen, the expression intensity of T-bet mRNA, ECP, and SIgE changed very little ( P ＞ 0.05). Conclusion Down-regulated expression of T-bet mRNA in mite-AR patients is not related to serum ECP and symptom scores but one of important links in the mechanism of imbalance of Th1/Th2 in the occurrence of AR. Specific allergen has no effect on T-bet mRNA, ECP, and SIgE of children and adults with AR in vitro. The level of SIgE objectively and directly indicates the severity of allergic symptom, but T-bet did not. T-bet may be one of indirect factors which affect the level of IgE.

Objective To summarize the outcomes of reconstructing right ventricular outflow tract with conical perucardial conduit in type Ⅲ pulmonary atresia with ventricular septal defect (PA/VSD).Methods We retrospectively analyzed the clinical data of 7 patients with type Ⅲ PA/VSD who underwent surgical repair in the Department of Cadiovascular Surgery,Guangdong Cardivascular Institute from January 2012 to August 2014.There were 3 males and 4 females at a median age of 2.5 years (range,1.4 to 10.8 years) and a mean weight of(11.4 ± 3.4) kg.All patients were underwent right ventricular outflow tract reconstruction with conical pericardial conduit.Results The mean bypass time was (132.7 ± 32.5) min,the mean aorta cross-clamping time was(71.9 ± 15.1) min.There was 1 patient with diaphragmatic paralysis and 1 patient with chylothorax,both of whom were underwent surgical intervention.There was 1 patient with postoperative pneumonia.The ventilation time was 17.8-356.9 hours.There was no in-hospital death.The mean ICU stays was 2.8-21.5 days and the mean hospital stays was 13-74 days.All patients were alive and no severe anoxia during follow-up.Conclusion The early outcomes of reconstructing right ventricular outflow tract with conical pericardial conduit in type Ⅲ PA/VSD was good.Preoperative evaluation of the pulmonary development and MAPCAs were helpful for making rational choice.

Objective To investigate the effects of p300/CBP on histone acetylation of Foxp3 gene and its roles in the immunological pathogenesis of Kawasaki disease (KD).Methods Forty-six children with KD and twenty-eight age-matched health children were consented to participate in this study.Co-immunoprecipitation and real-time PCR were performed to detect Foxp3-associated acetylation levels of histone H4 and binding abilities of p300, CBP, pSmad3 (phosphorylated mothers against decapentaplegic homolog 3) and NF-AT (nuclear factor of activated T cells) with Foxp3 gene in CD4+ T cells.The percentages of CD4+CD25high Foxp3+ cells (Treg) and the expression of Foxp3, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), p300, CBP, TGF-βRⅡ (transforming growth factor β receptor Ⅱ) and pLAT1 at protein level were analyzed by flow cytometry.Quantitative real-time PCR was used to measure the expression of Foxp3, IL-10, TGF-β, TGF-βRⅠ, Egr-1 (early growth response protein 1), RARα (retinoic acid receptor α) and PLCγ1 (phospholipase C-γ1) in Treg cells at mRNA level.Plasma concentrations of TGF-β and retinol acid (RA) were measured by enzyme-linked immunosorbent assay.Results (1) The percentages of Treg cells, levels of Foxp3 and molecules associated with suppressive function of Treg cells (TGF-β, IL-10 and CTLA4), acetylation levels of histone H4 associated with promoter, conserved non-coding DNA sequence 1 (CNS1) and CNS2 of Foxp3 gene decreased remarkably during acute KD (P<0.05), but were restored after IVIG therapy (P<0.05).Meanwhile, all of the aforementioned items in KD patients with coronary artery lesions (KD-CAL+) were lower than those without coronary artery lesions (KD-CAL-) (P<0.05).No significant differences in histone H4 acetylation associated with CNS3 were found among different groups (P>0.05).(2) The levels of p300 and CBP in Treg cells and their binding abilities with Foxp3 gene were down-regulated significantly during acute KD (P<0.05), but were restored to some extent after IVIG treatment (P<0.05).The Foxp3-associated histone acetylation was positively correlated with the expression of p300 and CBP at mRNA level during acute KD (r=0.65, 0.42, P<0.05).Furthermore, the expression of p300 and CBP and their binding abilities with Foxp3 gene in KD-CAL+ group were lower than those in KD-CAL-group (P<0.05).(3) Compared with healthy subjects, plasma concentrations of TGF-β and RA and the expression of TGF-βRⅠ/Ⅱ/Egr-1, RARα and pLAT1/PLCγ1 were down-regulated during acute KD (P<0.05);the binding abilities of pSmad3 and NFAT with Foxp3 gene were reduced remarkably in patients with acute KD (P<0.05).All the items mentioned above were restored after IVIG treatment (P<0.05).Moreover, the ten items aforementioned in KD-CAL+ group were lower than those in KD-CAL-group (P<0.05).(4) Higher acetylation levels of histone H4 associated with promoter, CNS1 and CNS2, and enhanced binding abilities of p300 and CBP with Foxp3 gene were found in CD4+ T cells isolated from patients with acute KD after co-stimulation with TGF-β, RA and anti-CD3/CD28 antibodies as compared with those in CD4+ T cells without stimulation (P<0.05).However, no statistical difference in the acetylation level of histone H4 associated with CNS3 was found between the two groups (P>0.05).Conclusion Hypoacetylation of histone H4 associated with Foxp3 gene caused by insufficient expression of p300/CBP and their impaired binding abilities might be involved with immune dysfunction in KD.IVIG therapy regulates the expression of p300/CBP and their binding abilities with Foxp3 gene through up-regulating TGF-β signal.

Objective To investigate the effects of SMYD3 and MLL5 on histone methylation of Transcription factor forkhead box protein 3 (Foxp3) gene and its roles in the immunological pathogenesis of Kawasaki disease (KD). Methods Forty-two children with KD and 26 age-matched healthy children were consented to participate in this study. Co-Immunoprec-ipitation and real-time polymerase chain reaction (PCR) was performed to determine Foxp3-associated histone methylation levels of H3K4me3 and H3K27me3, and binding levels of SMYD3 and MLL5 with Foxp3 gene in CD4+T cells. The proportion of CD4+CD25high Foxp3+cells (Treg) and protein levels of Foxp3, cytotoxic T lymphocyte associated antigen-4 (CTLA4), TGF-βRⅡand pSmad3 were analyzed by flow cytometry. Quantitative real-time PCR was used to evaluate levels of Foxp3, interleukin (IL)-10, GITR, TGF-βRⅠand RARαmRNA in CD4+T cells. Plasma concentrations of TGF-βand retinol acid (RA) were measured by enzyme-linked Immunosorbent assay. Independent-samples t-test was used as the statistical method in this study. Results ① The proportion of Treg, expression levels of Foxp3 and molecules associated with suppressive function of Treg cells(IL-10, GITR and CTLA4), and histone methylation levels of H3K4me3 associating with promoter, conserved non-coding DNA sequence (CNS) 1 and CNS2 of Foxp3 gene decreased remarkably during acute KD [Promoter:(5.4±1.8)%vs (9.1±2.2)%;CNS1:(2.6±0.9)% vs (3.8±1.1)%; CNS2: (2.4±0.8)% vs (4.2±1.0)%; t=5.50, 6.02, 9.56, 7.92, 7.97, 4.76, 7.73, 5.01, 8.66; P<0.05], and restored after intravenous immunoglobulins (IVIG) therapy [Promoter: (7.2 ±2.1)% vs (5.4 ±1.8)%; CNS1:(3.6±1.4)% vs (2.6±0.9)%; CNS2: (3.6±1.4)% vs (2.4±0.8)%; t=5.56, 4.59, 7.01, 6.04, 5.89, 4.83, 4.45, 4.00, 5.12; P<0.05]. Meanwhile, the nine former items in KD patients with coronary artery lesions (KD-CAL+) were lower than those without coronary artery lesions (KD-CAL-) [Promoter: (4.11±1.45)% vs (6.16±1.93)%; CNS1:(1.99±0.87)%vs (2.96±1.10)%;CNS2: (1.75±0.63)%vs (2.72±1.16)%;t=6.28, 3.24, 4.56, 3.69, 3.38, 4.40, 3.65, 3.00, 3.51; P<0.05]. No significant difference of H3K4me3 associated with CNS3 and H3K27me3 were found among the groups (t=1.03, 0.91, 1.48 and 0.79, 0.82, 1.53; P>0.05). ② Binding levels of SMYD3 and MLL5 with Foxp3 gene in CD4+T cells were down-regulated significantly during acute KD (t=6.63, 6.15; P<0.05), and restored to some extent after IVIG treatment (t=5.36, 4.56; P<0.05). Positive correlations between binding levels of SMYD3 and MLL5 and expression level of Foxp3 mRNA were detected in patients with acute KD (r=0.62、0.45, P<0.05). Furthermore, Binding levels of SMYD3 and MLL5 with Foxp3 gene in KD-CAL+group were lower than those in KD-CAL- group (t=4.11, 4.31; P<0.05). ③ Compared with healthy controls, plasma concentration of TGF-β and RA, and expressions of TGF-βRⅡ, TGF-βRⅠ, pSmad3 and RARα were down-regulated during acute KD (t=11.54, 12.81, 7.43, 16.10, 8.25, 12.06; P<0.05), and elevated remarkably after IVIG treatment (t=8.40, 6.24, 5.94, 11.78, 6.27, 8.30; P<0.05). Simultaneously, all the items aforementioned in KD-CAL+ group were found to be lower than those in KD-CAL-group (t=3.58, 3.30, 3.82, 5.27, 4.71, 3.78; P<0.05). Conclusion Hypomethylation of H3K4me3 associated with Foxp3 gene caused by insufficient binding levels of SMYD3/MLL5 may be involved with immune dysfunction in Kawasaki disease.

Objective To investigate the changes and significances of IL-17-associated histone methylation in the acute phase of Kawasaki disease (KD). Methods Forty-two children with KD and 28 age-matched healthy children were recruited in this study. Co-immunoprecipitation and real-time PCR were performed to detect the IL-17-associated histone methylation in CD4+ T cells. The percentages of CD4+IL-17+ T cells (Th17) and the expression of IL-17 and pSTAT3 at protein level were analyzed by flow cytome-try. Quantitative real-time PCR was used to measure the expression of IL-17, IL-6Rα, gp130, IL-23R, IL-23Rβ1, ETV5, SOCS1, SOCS3, TLR4, MyD88/TRIF, TNFR1 and RIP1 at mRNA level and the expres-sion of miR155 in CD4+ T cells. The levels of IL-6, IL-23 and TNF-αin plasma samples were measured by enzyme-linked immunosorbent assay. Results (1) The children with acute KD showed increased percenta-ges of Th17 cells and enhanced expression of IL-17 and H3K4me3, but inhibited expression of H3K27me3 [H3K4me3:(3.79±1. 45)% vs (1. 93±0. 31)%, H3K27me3: (54. 51±13. 60)% vs (73. 96± 22. 32)%;P<0. 05]. Moreover, the three former indexes in KD patients complicated with coronary artery lesions ( KD-CAL+) were higher than those in KD patients without coronary artery lesions ( KD-CAL-) , while the levels of H3K27me3 in KD-CAL+ group were lower than those in KD-CAL- group [ H3K4me3:(5. 11±1. 68)% vs (2. 98±0. 99)%, H3K27me3:(45. 02±14. 83)% vs (60. 35±12. 51)%;P<0. 05]. A positive correlation was observed between the ratio of H3K4me3/H3K27me3 and IL-17 at transcriptional level in patients with acute KD (r=0. 69, P<0. 05). Treatment with intravenous immunoglobulin (IVIG) restored Th17 cells, expression of IL-17 and methylation levels of H3K4me3 and H3K27me3 to normal levels [H3K4me3:(2. 44 ± 0. 77)% vs (3. 79 ± 1. 45)%, H3K27me3: (66. 52 ± 15. 73)% vs (54. 51 ± 13. 60)%;P<0. 05]. (2) The expressions of pSTAT3, ETV5 and miR155 increased significantly in pa-tients with acute KD, while the expressions of negative regulators of pSTAT3 ( SOCS1 and SOCS3 ) were down-regulated. The expressions of pSTAT3, ETV5 and miR155 in KD-CAL+ group were higher than those in KD-CAL- group (P<0. 05), while the levels of SOCS1 and SOCS3 in KD-CAL+ group were lower than those in KD-CAL- group (P<0. 05). IVIG therapy restored the indexes mentioned above to some extent (P<0. 05). (3) Compared with the healthy subjects, the levels of inflammatory cytokines (IL-6, IL-23 and TNF-α) in plasma and the expressions of surface receptors (TLR4, IL-6Rα/gp130, IL-23R/IL-23Rβ1 and TNFR1) and its downstream adaptors (MyD88, TRIF, RIP1) in CD4+T cells were up-regulated in patients with acute KD (P<0. 05), but were down-regulated significantly after IVIG treatment (P<0. 05). Moreo-ver, all of the indexes mentioned above in KD-CAL+ group were found to be higher than those in KD-CAL-group (P<0. 05). Conclusion Aberrant patterns of IL-17-associated histone methylation might be related to the immune dysfunction in patients with KD.

Objective To study the clinical feature,treatment,and prognosis of the cytomegalovirus (CMV)pneumonia patients treated with immunosuppressor against kidney disease.Mlethod The patients received immunosuppressor against kidney disease in The First Affiliated Hospital of Sun Yat-sen University from June 1999 to December 2006.CMV antigen of leucocyte in the peripheral blood and/or bronchoalveolar lavage fluid of these patients were detected with immunocytochemical methods,and 21 patients were found suffering from CMV pneumonia.The 21 patients were introvenously injected with ganciclovir 5～10 mg/(kg?d),and the immunosuppressive agent treatment suspended.Their clinical feature and prognosis were retrospectively analyzed. Results The 21 patients received corticosteroids before CMV pneumonia contracted,of them,13 patients had been intensively treated with Methyllprednisolone with mean total dose(3.2?0.6)g.Of them,15 had been treated with cyclophosphamide with mean total dose(3.8?1.3)g.The median time from the beginning of using immunosuppressor to the onset of CMV pneumonia was 25(13～92)days.All patients had fever,cough, shortness of breath and X-ray showed interstitial pneumonia,of them,19 patients developed hypoxemia,and 11 patients' CMV antigen was positive in the leucocyte from bronchial lavage fluid.The result showed 9 patients survived and 12 died.The average duration of treatment with ganciclovir was(26.2?6.3)days. CMV pneumonia is a serious complication in patients who were treated with immunosuppressor against kidney disease.The mortality is high.Ganciclovir is a medicine of choice to treat CMV pneumonia.

Four new triterpenoids, together with six known analogues, were isolated from an aqueous extract of the Ziziphus jujuba var. spinosa seeds, by multiple column chromatographic separation methods using stationary phases of macroporous adsorption resin, MCI resin, normal phase silica gel, Sephadex LH-20, and Toyopearl HW-40C as well as preparative thin-layer chromatography and reversed-phase HPLC. Their structures were determined by spectroscopic data analysis, the new structures were trivially named jujubaceanothoside A (1), 23-epijujuboside A (2), and jujubosides J and K (3 and 4), while the known analogues were identified as jujubosides A-C (5-7) and II (8), alphitolic acid (9), and betulinic acid (10). The structure of 1 was confirmed by single crystal X-ray diffraction.

Plant active components characterized of many different structures and activities on multiple targets, have made them to be the important sources of inhibitors on HIV-1. For finding leading compounds with new structure against HIV-1, three key HIV-1 replicative enzymes (reverse transcriptase, protease and integrase) were used as screening models. The in vitro activities of 45 plant derived components isolated from Schisandraceae, Rutaceae and Ranunculaceae were reported. Within twelve triterpene components isolated, eight compounds were found to inhibit HIV-1 protease, in these eight active compounds, kadsuranic acid A (7) and nigranoic acid (8), inhibited both HIV-1 protease and integrase; Among fifteen lignans, meso-dihydroguaiaretic acid (15) and kadsurarin (16) were active on HIV-1 reverse transcriptase, and 4, 4-di(4-hydroxy-3-methoxyphenly)-2, 3-dimethylbutanol (13) active on HIV-1 integrase. All of the six alkaloids, seven flavones, and five others compounds were not active or only with low activities against HIV-1 replicative enzymes. Further studies of the triterpene components showing strong inhibitory activities on HIV-1 were warranted.
Alkaloids ; chemistry ; isolation & purification ; pharmacology ; Anti-HIV Agents ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Flavones ; chemistry ; isolation & purification ; pharmacology ; Guaiacol ; analogs & derivatives ; chemistry ; isolation & purification ; pharmacology ; HIV Integrase ; drug effects ; HIV Protease ; drug effects ; HIV Reverse Transcriptase ; antagonists & inhibitors ; Lignans ; chemistry ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Ranunculaceae ; chemistry ; Rutaceae ; chemistry ; Schisandraceae ; chemistry ; Triterpenes ; chemistry ; isolation & purification ; pharmacology